Manufacturing the Biopharmaceutical Drug Product

Abstract

Manufacture of the finished drug product is the last process step (from starting materials to drug substance and now to drug product) for the biopharmaceutical. Biopharmaceuticals are typically packaged as sterile injectables; therefore, biopharmaceutical drug product manufacturing requires strict adherence to cGMPs, appropriate and adequate aseptic processing, and tight control of the filling process parameters. At times, before the drug product process begins, the purified bulk drug substance is conjugated (e.g., antibody drug-conjugates (ADCs), PEGylation), and these bioconjugation manufacturing process steps are also examined in this chapter. The two main process stages for the drug product are discussed in this chapter: (1) formulation (if excipients are not already present in the bulk drug substance), and (2) aseptic filling and sealing into an appropriate container closure system. Drug product manufacturing for both the protein-based biopharmaceuticals (recombinant proteins and monoclonal antibodies) and the gene therapy-based biopharmaceuticals (viral vectors, genetically modified patient cells) is the focus of this chapter. Comments will also be made on combination products, which involve the use of a device as a container closure. Application, where appropriate, for the minimum CMC regulatory compliance continuum risk-based approach will be discussed.